Heterocyclic ureas such as N-benzimidazolyl, N-benzothiazolyl or N-benzoxazolyl-N'-phenyl ureas are useful as immune regulants and anti-viral compounds according to Paget et al., J. Med. Chem., 12, 1010 (1969); 1016 (1969). These N-heterocyclic-N'-phenyl ureas can be substituted in either the phenyl moiety of the heterocyclic benzothiazole, benzoxazole or benzimidazole ring with substituents such as halo, alkoxy, alkyl, carboethoxy, trifluoromethyl, nitro and the like, or in the N'-phenyl group with substituents such as chloro, fluoro, nitro, methyl, trifluoromethyl, bromo and the like. Compounds which contain a hydroxy group as a substituent in the phenyl portion of the heterocyclic nucleus have not been prepared. Obvious methods of preparing such a 6-hydroxy derivative have been found not to be operative; for example, the corresponding 6-methoxy compound is not readily demethylated by the use of 50 percent HBr or other standard demethylating reagent. In addition, carrying out the standard synthesis of benzimidazolyl, benzoxazolyl or benzothiazolyl ureas involving the reaction of an isocyanate with a 2-amino-substituted benzimidazole, benzoxazole or benzothiazole, having a benzyloxy substituent in the phenyl moiety of the heterocyclic ring also did not provide an operative procedure for preparing the corresponding hydroxy compound since the benzyl group proved to be extremely resistant to debenzylation using hydrogenation conditions involving a palladium catalyst. N-2-(6-hydroxybenzothiazolyl)-N'-phenyl urea was, however, discovered as a metabolic product in urine when the corresponding 6-methoxy compound was fed to rats. A complex procedure for preparing this compound involving the use of trimethylsilyl chloride has been devised, as fully set forth in the copending application of Paget and Wikel, Ser. No. 502,129 filed this even date.
It is an object of this invention to provide an improved method for preparing N-2-(6-hydroxybenzothiazolyl)-N'-phenyl (or substituted-phenyl) ureas, which improved method is more adaptable to industrial production than methods heretofore available and which avoids the use of expensive reagents.